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Age-Dependent morphine tolerance development in the rat

Authors
 Yan Wang  ;  James Mitchell  ;  Kumi Moriyama  ;  Ki-jun Kim  ;  Manohar Sharma  ;  Guo-xi Xie  ;  Pamela Pierce Palmer 
Citation
 ANESTHESIA AND ANALGESIA, Vol.100(6) : 1733-1739, 2005 
Journal Title
 ANESTHESIA AND ANALGESIA 
ISSN
 0003-2999 
Issue Date
2005
MeSH
Aging/physiology* ; Analgesics, Opioid/pharmacokinetics ; Analgesics, Opioid/pharmacology* ; Animals ; Chromatography, High Pressure Liquid ; Drug Tolerance/physiology* ; Male ; Mass Spectrometry ; Morphine/pharmacokinetics ; Morphine/pharmacology* ; Morphine Derivatives/blood ; Pain Measurement/drug effects ; Rats ; Rats, Sprague-Dawley ; Reaction Time/drug effects
Keywords
15920206
Abstract
In all age groups, the use of opioids to treat chronic pain conditions has increased, yet the impact of age on opioid tolerance development has not been comprehensively addressed. In this study, we investigated age-related differences in morphine tolerance development in rats. Rats aged 3 wk, 3 mo, 6 mo, and 1 yr were used in the study. Morphine (8 mg/kg) was injected subcutaneously twice each day and its analgesic effect assessed by the change in tail-flick latency using a thermal stimulus 5 min before and 30 min after dosing. Tolerance was defined as a 75% reduction in morphine-induced analgesia compared to Day 1. Rats aged 3 wk, 3 mo, 6 mo, and 1 yr developed tolerance on the 4th, 10th, 14th, and 22nd days of morphine treatment, respectively. Plasma levels of morphine and its metabolites showed that pharmacokinetic differences among the groups did not correlate with the differences in tolerance development. This study demonstrates that morphine tolerance occurs more rapidly in younger rats than older rats and is unlikely to be the result of differences in drug metabolism or clearance. Aging may impact molecular processes involved in tolerance development and provide insight into novel therapeutic targets to delay opioid tolerance development.
Full Text
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00000539-200506000-00033&LSLINK=80&D=ovft
DOI
10.1213/01.ANE.0000152192.23851.40
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ki Jun(김기준) ORCID logo https://orcid.org/0000-0003-1950-7998
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151139
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